Le iperossalurie primitive: elementi di diagnostica clinica e metabolica.

Primary hyperoxalurias (PH) are autosomal recessive metabolic disorders, characterised by overproduction and urinary excretion of oxalate, presenting with nephrolithiasis, nephrocalcinosis and kidney failure. Plasma oxalate is higher than normal in PH, and it rises further in renal failure. When glomerular filtration rate falls below 30 mL/min /1.73m2, oxalate levels increase sharply and plasma becomes supersaturated with calcium oxalate, which precipitates in body tissues (systemic oxalosis). Three types of PH are described; the most frequent is PH1 (70-80%), due to deficiency of L-alanine:glyoxylate aminotransferase (AGT), the enzyme which catalyses in hepatocytes the transamination of alanine and glyoxylate to pyruvate and glycine. That leads to accumulation of glyoxylate, which is converted both in oxalate (by lactate dehydrogenase, LDH) and glycolate (by glyoxylate reductase). Increased levels of glycolate, both in serum and urine, are the hallmark of PH1. PH2 is due to variants of gene encoding for the enzyme glyoxylate and hydroxypyruvate reductase (GRHPR), which converts both glyoxylate to glycolate and hydroxypiruvate to D-glycerate in many tissues. Pathologic variants of GRHPR gene induce increased levels of glyoxylate and hydroxypyruvate, converted by LDH to oxalate and L-glycerate respectively. High levels of glycerate, both in serum and urine, allow the metabolic diagnosis of PH2. PH3 is due to variants of HOGA gene, which catalyses the cleavage of 4-hydroxy-2- oxoglutarate (HOG) to pyruvate and glyoxylate. Increased levels of both HOG and 4-hydroxy glutamate are metabolic hallmark of PH3. In this paper, an overview of oxalate metabolism was reported, and the main features of the pathophysiology, diagnosis, clinical course and treatment of PH as well. [ABSTRACT FROM AUTHOR]